Psychotropic drugs represents a special safety problem as the patients due to their psychological disorders are more prone to accidential or deliberate overdosing than other groups of patients. Most of the drugs used in the treatment of severe depressions are for example potentially lethal in doses that are available to patients with a high risk of suicide.
Table 1, obtained from the data system SWEDIS covering the Swedish market, may serve as an example to illustrate that deaths from overdosage of psychotropic drugs are a common problem.
The risk of suicide with antidepressants have, for example, been discussed in detail by Montgomery et al. (S. A. Montgomery, M. T. Lambert and S. P. J. Lynch,
The Risk of Suicide with Antidepressants, International clinical psychopharmacology, Suppl. 2, 15-24, 1988) including mortality rates and problems associated with treatment of patients who have episodes of deliberate self-harm due to depression or personality disorders. Psychotropic agents can be divided in different groups such as antidepressants, antipsychotic agents, anxiolytic agents and, hypnotic and sedative agents. Significant toxic effects of antidepressant agents of the tricyclic or tetracyclic type such as clomipramine, imipramine, amipramine, desipramine, nortriptyline, dothiepin or maprotline are, for example, relatively common and estimates of prevalence have run as high as 5% (adapted from Goodman and Gilman's The Pharmacological Basis of Therapeutics, Seventh Edition, Macmillan Publishing Comp., New York, 1985). Clinical consequences of the antimuscarin effects are e.g. dry mouth, epigastrial distress, constipation, dizziness, tachycardia, palpitation, blurred vision and urinary retention. In addition tricyclic antidepressive agents may give rise to manic reactions and cases of confusion and delirium are common especially among elderly patients.
Acute poisoning with tricyclic and tetracyclic antidepressants is common and often life threatening. Patients suffering from severe depression have a high risk of suicide and have often access to potentially lethal doses of antidepressants. The risk can be reduced to some extent by not dispensing more than e.g. a weeks supply of an antidepressant to an acutely depressed patient. It is well known from medical praxis that it will in general take 2-3 weeks before substantial improvements are obtained. The symptoms may even be aggravated during the first phase of the treatment. This initial part of the treatment will consequently be a large problem regarding the safety of the patient.
The antipsychotic drugs have in general a high therapeutic index and are considered as relatively safe agents. Occasional deaths from overdosage have been reported however, especially when the drugs have been ingested concurrently with alcohol or other drugs. Antipsychotic or neuroleptic drugs potentiate e.g. the action of other central-nervous system depressants and extreme care has therefore been recommended if a need arises to use them concurrently with alcohol, hypnotics such as barbiturates, narcotic analgetics or general anesthetics.
The benzodiazepines, from the group hypnotic agents and sedatives and the group of anxiolytic agents, are considered as relatively safe drugs but overdosage is sometimes fatal. Alcohol is a common contributor to deaths involving benzodiazepines. The safety risks are consequently not restricted to antidepressants but should be considered also for other groups of psychotropic agents.
Tricyclic and tetracyclic antidepressants represents, from a chemical point of view, a rather well characterized group including in general cyclic structures and a substituted chain including at least one aminogroup. Amines are basic substances that can form complexes with cationic exchangers. Substances that includes ionizable groups such as amines, aromatic alcohols and carboxylic acids can form complexes with anionic or cationic ion exchangers, below refered to as ion exchange resins.